! PROJECT SUMMARY ! This application is requesting funds to purchase a Q ExactiveTM HF-X Hybrid Quadrupole-OrbitrapTM Mass Spectrometer (QE HF-X) from Thermo Fisher Scientific. The proposed instrument will be located in the Mass Spectrometry Proteomics Core at Baylor College of Medicine (BCM). The predominant use of the QE HF-X will be proteome profiling of patient samples, pre-clinical patient-derived xenograft (PDX) cancer models, and various animal- and cell-based models of disease. These user projects have large sample cohorts that require deep-coverage proteome profiling assays with fast sequencing rates and robust performance over time. An improved ion transmission pass and a fast high mass resolution and mass accuracy analyzer platform of the QE HF-X is ideal for high throughput quantitative proteomics, which makes this mass spectrometer best suited and the most cost-effective instrument for the proposed studies. The ultimate and unifying goal of the projects selected for QE HF-X supported service is to understand the molecular mechanisms that regulate biological processes in normal and disease states. This instrument will offer maximum capabilities as well as maximum flexibility to best serve the evolving needs of the diverse BCM investigators. Expansion of the proteomics research is an essential component of the college's strategic plan, where a broad base of health professionals and biomedical research faculty is aiming to understand underlining biology and develop new therapies for treatments of cancer, metabolic disease, and other disorders. The QE HF-X instrument ? a critically needed addition to our existing instrumentation capacity ? combined with the most advanced miniaturized proteome profiling platform developed by our proteomics group will enable expansion of research opportunities and directions at BCM and neighboring Texas Medical Center institutions.